Analgesic potency of mu and kappa opioids after systemic administration in amphibians.
ABSTRACT The relative analgesic potency of 11 opioid agents was assessed by using the acetic acid test in amphibians. Systemic administration of the mu agonists, fentanyl, levorphanol, methadone, morphine, meperidine and codeine; the partial mu agonist, buprenorphine; and the kappa agonists nalorphine, bremazocine, U50488 and CI-977 was made by s.c. injection into the dorsal lymph sac of the Northern grass frog, Rana pipiens. All agents produced a dose-dependent and long-lasting analgesia which persisted for at least 4 hr. The analgesic effects of single doses of each agent were significantly blocked or reduced by pretreatment with naltrexone. Systemic opioids produced log dose-response curves which yielded ED50 values ranging from 1.4 nmol/g for fentanyl to 320.9 nmol/g for nalorphine. Comparison of ED50 values gave a rank order of analgesic potency = fentanyl > CI-977 > levorphanol > U50488 > methadone > bremazocine > morphine > buprenorphine > meperidine > codeine > nalorphine. The relative analgesic potency of mu opioids in amphibians was significantly correlated with relative analgesic potency of these same agents obtained on the mouse writhing and hot plate tests. These data suggest that the amphibian model may serve as an adjunct or alternative model for the testing of opioid agents. Furthermore, given the inactivity of kappa opioids on rodent hot plate and tail-flick tests, the acetic acid test in amphibians may be especially well-suited for the assessment of opioid analgesia after administration of kappa-selective opioids.
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ABSTRACT: Objective-To identify pain-related behaviors and assess the effects of butorphanol tartrate and morphine sulfate in koi (Cyprinus carpio) undergoing unilateral gonadectomy. Design-Prospective study. Animals-90 adult male and female koi. Procedures-Each fish received saline (0.9% NaCl) solution (which is physiologically compatible with fish) IM, butorphanol (10 mg/kg [4.5 mg/lb], IM), or morphine (5 mg/kg [2.3 mg/lb], IM) as an injection only (6 fish/treatment); an injection with anesthesia and surgery (12 fish/treatment); or an injection with anesthesia but without surgery (12 fish/treatment). Physiologic and behavioral data were recorded 12 hours before and at intervals after treatment. Results-Compared with baseline values, the saline solution-surgery group had significantly decreased respiratory rates (at 12 to 24 hours), food consumption assessed as a percentage of floating pellets consumed (at 0 to 36 hours), and activity score (at 0 to 48 hours). Respiratory rate decreased in all butorphanol-treated fish; significant decreases were detected at fewer time points following morphine administration. In the butorphanol-surgery group, the value for food consumption initially decreased but returned to baseline values within 3 hours after treatment; food consumption did not change in the morphine-surgery group. Surgery resulted in decreased activity, regardless of treatment, with the most pronounced effect in the saline solution-surgery group. Changes in location in water column, interactive behavior, and hiding behavior were not significantly different among groups. Butorphanol and morphine administration was associated with temporary buoyancy problems and temporary bouts of excessive activity, respectively. Conclusions and Clinical Relevance-Butorphanol and morphine appeared to have an analgesic effect in koi, but morphine administration caused fewer deleterious adverse effects. Food consumption appeared to be a reliable indicator of pain in koi.Journal of the American Veterinary Medical Association 09/2013; 243(6):882-90. · 1.72 Impact Factor
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ABSTRACT: Immersion anaesthetic techniques are commonly used in amphibian species. Alfaxalone has been reported as an immersion anaesthetic in fish but not amphibians. CASE HISTORY AND EXAMINATION: A Mexican 56 g axolotl was presented with a 3-day history of anorexia. Anaesthesia was required for the surgical retrieval of two gastric foreign bodies. Prior to anaesthesia, on visual inspection the axolotl was bright and active. Branchial and gular respiratory movements occurred at approximately 24 respirations minute(-1) and heart rate was approximately 52 beats minute(-1) . The axolotl was exposed to increasing concentrations (up to 5 mg L(-1) ) of alfaxalone (Alfaxan; Vetóquinol, UK) in a water bath. After becoming sedated the axolotl was removed from the water bath. Anaesthesia was induced and maintained with alfaxalone (5 mg L(-1) ) via continuous irrigation of the gills (branchial) and skin (cutaneous) with additional 30 μL drops of alfaxalone (10 mg mL(-1) ) administered branchially as required. Endoscopy and surgery were performed to remove two gastric foreign bodies. Branchial and gular respiratory movements persisted at what was considered an appropriate anaesthetic depth. Anaesthetic depth could be rapidly deepened by branchial irrigation of alfaxalone solutions and lightened by irrigation using fresh water. Anaesthesia lasted approximately 1 hour and recovery was rapid (within 15 minutes). Recovery was assisted through branchial and cutaneous irrigation with fresh water. No obvious adverse effects of anaesthesia were observed immediately post-anaesthesia or, according to the owner, in the following week. Conclusions Axolotls can be anaesthetized using alfaxalone administered via immersion and branchial/transcutaneous irrigation offering an alternative technique for anaesthetising axolotls for clinical and research purposes.Veterinary Anaesthesia and Analgesia 11/2011; 38(6):619-23. · 1.34 Impact Factor
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ABSTRACT: Preclinical studies of analgesia in amphibians or recommendations for clinical use of analgesics in amphibian species are extremely limited. This article briefly reviews the issues surrounding the use of analgesics in amphibians, starting with common definitions of pain and analgesia when applied to nonhuman animals. Nociceptive and endogenous opioid systems in amphibians are reviewed, and results of preclinical research on opioid and nonopioid analgesics summarized. Recommended opioid and nonopioid analgesics are summarized, and practical recommendations made for their clinical use.Veterinary Clinics of North America Exotic Animal Practice 01/2011; 14(1):33-44.